{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:29:14Z","timestamp":1785212954792,"version":"3.55.0"},"reference-count":47,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T00:00:00Z","timestamp":1576022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007437","name":"TrygFonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007437","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005275","name":"Capital Region of Denmark","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001732","name":"Danish National Research Foundation","doi-asserted-by":"publisher","award":["DNRF55"],"award-info":[{"award-number":["DNRF55"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001732","name":"Danish National Research Foundation","doi-asserted-by":"publisher","award":["09-067009"],"award-info":[{"award-number":["09-067009"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001732","name":"Danish National Research Foundation","doi-asserted-by":"publisher","award":["09-075724"],"award-info":[{"award-number":["09-075724"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["01GI0925"],"award-info":[{"award-number":["01GI0925"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["21435006"],"award-info":[{"award-number":["21435006"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21874130"],"award-info":[{"award-number":["21874130"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The liver is crucial to maintain energy homeostasis during exercise. Skeletal muscle-derived metabolites can contribute to the regulation of hepatic metabolism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We aim to elucidate which metabolites are released from the working muscles and taken up by the liver in exercising humans and their potential influence on hepatic function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In two separate studies, young healthy men fasted overnight and then performed an acute bout of exercise. Arterial-to-venous differences of metabolites over the hepato-splanchnic bed and over the exercising and resting leg were investigated by capillary electrophoresis- and liquid chromatography-mass spectrometry metabolomics platforms. Liver transcriptome data of exercising mice were analyzed by pathway analysis to find a potential overlap between exercise-regulated metabolites and activators of hepatic transcription.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>During exercise, hepatic O2 uptake and CO2 delivery were increased two-fold. In contrast to all other free fatty acids (FFA), those FFA with 18 or more carbon atoms and a high degree of saturation showed a constant release in the liver vein and only minor changes by exercise. FFA 6:0 and 8:0 were released from the working leg and taken up by the hepato-splanchnic bed. Succinate and malate showed a pronounced hepatic uptake during exercise and were also released from the exercising leg. The transcriptional response in the liver of exercising mice indicates the activation of HIF-, NRF2-, and cAMP-dependent gene transcription. These pathways can also be activated by succinate.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Metabolites circulate between working muscles and the liver and may support the metabolic adaption to exercise by acting both as substrates and as signaling molecules.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgz266","type":"journal-article","created":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T16:39:56Z","timestamp":1576082396000},"page":"1196-1209","source":"Crossref","is-referenced-by-count":42,"title":["Muscle-Liver Substrate Fluxes in Exercising Humans and Potential Effects on Hepatic Metabolism"],"prefix":"10.1210","volume":"105","author":[{"given":"Chunxiu","family":"Hu","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Hoene","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry and Pathobiochemistry, University Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Plomgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark"},{"name":"The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases and CMRC, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob S","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark"},{"name":"The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Department of Infectious Diseases and CMRC, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjie","family":"Zhao","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry and Pathobiochemistry, University Tuebingen, Tuebingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Dalian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens O","family":"Clemmesen","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels H","family":"Secher","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, The Copenhagen Muscle Research Centre, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans U","family":"H\u00e4ring","sequence":"additional","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum Muenchen at the University of Tuebingen, Otfried-Mueller-Strasse, Tuebingen, Germany"},{"name":"German Center for Diabetes Research (DZD), Ingolst\u00e4dter Landstrasse, Oberschleissheim, 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